title: Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.
abstract: Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.
authors.affiliation: 1] Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands [2] Department of Psychiatry, ZNA hospitals, Antwerp, Belgium.
authors.forename: J J
authors.initials: JJ
authors.lastname: Luykx
authors.forename: S C
authors.initials: SC
authors.lastname: Bakker
authors.forename: N
authors.initials: N
authors.lastname: van Geloven
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: S
authors.initials: S
authors.lastname: Horvath
authors.forename: E
authors.initials: E
authors.lastname: Lentjes
authors.forename: M P M
authors.initials: MP
authors.lastname: Boks
authors.forename: E
authors.initials: E
authors.lastname: Strengman
authors.forename: J
authors.initials: J
authors.lastname: DeYoung
authors.forename: J E
authors.initials: JE
authors.lastname: Buizer-Voskamp
authors.forename: R M
authors.initials: RM
authors.lastname: Cantor
authors.forename: A
authors.initials: A
authors.lastname: Lu
authors.forename: E P A
authors.initials: EP
authors.lastname: van Dongen
authors.forename: P
authors.initials: P
authors.lastname: Borgdorff
authors.forename: P
authors.initials: P
authors.lastname: Bruins
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.forename: R A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D000328:Adult; D000483:Alleles; D003863:Depression / Q000134:cerebrospinal fluid* / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012621:Seasons; D012701:Serotonin / Q000134:cerebrospinal fluid* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid